ModifiedEmblemHealthPolicy MG.MM.PH.95

Medical Policy: Colony Stimulating Factors

Defines medical necessity, preferred vs non-preferred filgrastim products (Neupogen, Granix, Nypozi, Releuko, Zarxio) for commercial, Medicaid and Medicare members, applicable indications, dosing unit limits, length of authorization, billing codes and ICD-10 diagnoses.

Policy Summary

PayerEmblemHealth

PolicyMedical Policy: Colony Stimulating Factors

Policy CodePolicy MG.MM.PH.95

Change TypeMaterial modifications to agent list, indications, and codes

Effective Date

Next Review Date

Key ActionTreating physician or PCP must submit clinical evidence that the member meets criteria for treatment; without documentation EmblemHealth will not review the request.

SourceLink

POLICY UPDATE CHANGES

Add Nypozi (filgrastim-txid) as a non-preferred agent to criteria.

Add Zarxio to Hematopoietic Subsyndrome of Acute Radiation Syndrome.

Annual Review: Removed J3590, Added Q5125, added NDCs: 63459-0918-xx and 63459-0920-xx (3/21/2024).

Initial Criteria: Myelodysplastic Syndrome criteria added (9/14/2023).

Added Releuko to affected agents (5/12/2022).

Extended coverage duration from 4 to 6 months (effective 01/01/2021).

5Filgrastim agents listed (Neupogen, Granix, Nypozi, Releuko, Zarxio)

3Max unit tiers (Severe Chronic Neutropenia / BMT or PBPC or Radiation / Other)

6Months authorization length

This EmblemHealth coverage policy addresses Colony Stimulating Factors (filgrastim products) including Neupogen, Granix, Nypozi, Releuko and Zarxio and applies to Commercial, Medicaid and Medicare members. The policy has a mixed coverage stance: Granix and Zarxio are preferred agents while Neupogen, Releuko and Nypozi are designated non-preferred and require step therapy or documented contraindication/intolerance to preferred agents for coverage.

Authorization is provided for a 6-month period and may be renewed. The policy specifies maximum billable unit tiers by indication: Severe Chronic Neutropenia: 1380 units/day, BMT/PBPC/Radiation: 1200 units/day, and All other indications: 600 units/day.

Policy-relevant thresholds and key stats

Threshold: Severe chronic neutropenia (ANC)ANC < 500/mm3

Preexisting neutropenia (prophylactic co-morbidity)ANC ≤ 1000/mm3

Myelodysplastic syndrome endogenous EPOEPO ≤ 500 mUnits/mL

Renal dysfunction (co-morbidity)Creatinine clearance < 50 mL/min

Liver dysfunction (co-morbidity)Bilirubin > 2.0 mg/dL

Max billable units per day (by indication)Severe chronic neutropenia: 1380 units/day; BMT/PBPC/Radiation: 1200 units/day; Other indications: 600 units/day

Authorization length6 months (coverage will be provided for six months and may be renewed)

Coding

Applicable HCPCS/CPT/HCPCS CodesHCPCS|mixed

J1442	Injection, filgrastim (G-CSF), excludes biosimilars, 1 microgram (1 mcg = 1 billable unit)
J1447	Injection, tbo-filgrastim (Granix), 1 microgram (1 mcg = 1 billable unit)
Q5101	Injection, filgrastim-sndz (Zarxio), biosimilar, 1 microgram (1 mcg = 1 billable unit)
Q5125	Injection, filgrastim-ayow (Releuko), biosimilar, 1 microgram (1 mcg = 1 billable unit)
C9173	Injection, filgrastim-txid (Nypozi), biosimilar, 1 microgram (1 mcg = 1 billable unit)

Applicable NDCsNDC

55513-0530-xx	Neupogen 300 mcg vial
55513-0924-xx	Neupogen 300 mcg SingleJect
55513-0546-xx	Neupogen 480 mcg vial
55513-0209-xx	Neupogen 480 mcg SingleJect
63459-0910-xx	Granix 300 mcg prefilled syringe
63459-0912-xx	Granix 480 mcg prefilled syringe
63459-0918-xx	Granix 300 mcg single-dose vial
63459-0920-xx	Granix 480 mcg single-dose vial
61314-0318-xx	Zarxio 300 mcg prefilled syringe
61314-0326-xx	Zarxio 480 mcg prefilled syringe

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Applicable ICD-10 DiagnosesICD-10

C92.00	Myeloid leukemia not having achieved remission
C92.02	Myeloid leukemia in relapse
C92.50	Acute myelomonocytic leukemia not having achieved remission
C92.52	Acute myelomonocytic leukemia in relapse
C92.60	Acute myeloid leukemia with 11q23-abnormality not having achieved remission
C92.62	Acute myeloid leukemia with 11q23-abnormality in relapse
C92.A0	Acute myeloid leukemia with multilineage dysplasia not having achieved remission
C92.A2	Acute myeloid leukemia with multilineage dysplasia in relapse
C93.00	Acute monoblastic/monocytic leukemia not having achieved remission
C93.02	Acute monoblastic/monocytic leukemia in relapse

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Provider Actions & Billing

Prior Authorization

Prior authorization and clinical documentation required

Treating physician or PCP must submit clinical evidence that the member meets the criteria for treatment. Requests submitted without the required clinical documentation will not be reviewed (preauthorization or post-payment).

Step Therapy

Step therapy for non-preferred agents

Non-preferred agents (Neupogen, Releuko, Nypozi) require step therapy: coverage for Neupogen, Releuko, or Nypozi is permitted only when the patient has a contraindication or severe intolerance to the preferred agents Granix AND Zarxio. This step therapy requirement applies to Commercial, Medicaid, AND Medicare members.

Billing Rule

Length of authorization

Authorization is granted for a six-month period. Coverage may be renewed per the renewal criteria (renewal mirrors initial criteria).

Billing Rule

Max billable units per day by indication

Maximum billable units per day vary by indication as listed below. Applicable HCPCS/Codes: see items.

J1442
J1447
Q5101
Q5125
C9173

Denial Risk

Denial if indication not listed

Neupogen is not considered medically necessary for indications other than those listed in the policy due to insufficient evidence of therapeutic value; claims may be denied if the submitted indication does not meet the policy criteria.

Documentation Required

Clinical evidence supporting indication-specific criteria

For prophylactic use, expected incidence thresholds for febrile neutropenia should reference the NCCN Myeloid Growth Factors guideline to establish regimen risk. The treating physician must reference clinical evidence (for example NCCN guidance) when attesting that the patient meets the indication-specific criteria.

Background & Evidence

EmblemHealth established these clinical review criteria after reviewing peer-reviewed literature, regulatory status and prescribing information, evidence-based guidelines from national organizations (including NCCN and ASCO), relevant compendia, and expert clinical opinion. The guideline text states the criteria reflect how EmblemHealth determines medical necessity and may be revised as new clinical information emerges.

The purpose of the policy is to govern management of filgrastim products, including designation of preferred agents (Granix, Zarxio), step therapy requirements for non-preferred agents, and to define covered indications consistent with FDA-labeled uses and Compendia-recommended indications (e.g., BMT, PBPC mobilization, prophylaxis and treatment of chemotherapy-induced febrile neutropenia, severe chronic neutropenia, AML post-induction/consolidation, myelodysplastic syndrome, and hematopoietic subsyndrome of acute radiation syndrome).

Source	Reference
NCCN Myeloid Growth Factors	Referenced for expected incidence of febrile neutropenia thresholds (NCCN Myeloid Growth Factors Clinical Practice Guideline)
ASCO guideline (J Clin Oncol. 2015)	Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update, J Clin Oncol. 2015
Neupogen prescribing information / package insert	Neupogen [package insert] (Amgen); referenced in policy references
Releuko prescribing information / package insert	Releuko® subcutaneous or intravenous injection [prescribing information] (Amneal); February 2022
Nypozi prescribing information / package insert	Nypozi [package insert] (Tanvex BioPharma USA, Inc.); June 2024
Zarxio prescribing information / package insert	Zarxio referenced as preferred agent and included for Radiation Syndrome (policy lists Zarxio; prescribing information cited in references)

ANC (Absolute neutrophil count): Laboratory measure used to define neutropenia; thresholds in policy include ANC < 500/mm3 for severe chronic neutropenia and ANC ≤ 1000/mm3 as a prophylactic co-morbidity.

BMT (Bone marrow transplant): FDA‑labeled indication for filgrastim use and included among covered transplant-related indications.

PBPC (Peripheral Blood Progenitor Cell): Indication for mobilization and transplant (policy notes PBPC indication excludes Releuko).

G-CSF (Granulocyte Colony Stimulating Factor): Class term for filgrastim products (includes Neupogen, Granix, Zarxio, Releuko, Nypozi) referenced throughout the policy.

Name	Number	Type	Effective Date
Human Granulocyte/Macrophage Colony Stimulating Factors (examples cited)	L34699	LCD
G-CSF (Neupogen®, Granix™, Zarxio™)	L34002	LCD	7/5/2016 (per source L34002 listing)
White Cell Colony Stimulating Factors	L37176	LCD	2/26/2018 (per source L37176 listing)

Revision History

1/15/2025addedLatest

Add Nypozi (filgrastim-txid) as a non-preferred agent to criteria.

1/15/2025addedLatest

Add Zarxio to Hematopoietic Subsyndrome of Acute Radiation Syndrome.

3/21/2024revised

Annual Review: Removed J3590, Added Q5125, added NDCs: 63459-0918-xx and 63459-0920-xx.

9/14/2023added

Initial Criteria: Myelodysplastic Syndrome criteria added (included IPSS-R lower risk, EPO ≤500, symptomatic anemia without del(5q), concurrent ESA therapy).

5/12/2022added

Added Releuko to affected agents.

01/01/2021revised

Extended coverage duration from 4 to 6 months (Length of Authorization).

OpenPayer

Medical Policy: Colony Stimulating Factors

Coverage Summary

Medical-Necessity Criteria

Coding

Provider Actions & Billing

Background & Evidence

Medicare Determinations

Revision History